- From early in MS, nerve degeneration in the brain can cause very slight, gradual loss of brain tissue.
- These small changes can predict worsening of disability in large studies but are hard to measure accurately over time using whole-brain MRI, and don’t necessarily reflect disease progression within an individual.
- One alternative to monitor individual disease progression may be to measure the expansion of spaces inside the brain, called the ventricles, as an indicator of central brain tissue loss.
- A new study has examined how this measure relates to damage in MS lesions and whole brain loss, towards personalised monitoring of changes in the brain.
MRI measures lesions and loss of brain tissue
Magnetic resonance imaging (MRI) is used to detect and monitor MS lesions. These are areas of damage or scarring in the brain and spinal cord caused by the immune system attacking the myelin sheath around nerves. These are usually seen on MRI as small circular spots of damage, and new lesions often occur as part of MS relapses.
Alongside this process in MS, there can be a gradual loss of nerves and brain tissue (“brain atrophy”), even in parts of the brain that otherwise look normal on MRI. In studies with a large number of participants, whole-brain loss predicts worsening of disability and cognition. However, experts have cautioned against using whole-brain loss to measure disease progression in individuals, as it can be difficult to standardise measurement over time, and other factors, such as dehydration, ageing, and other medical conditions, can also affect brain size.
Alternative MRI measures of neurodegeneration in MS
Despite these hurdles, there is a growing demand for MRI measures of MS progression in the clinic to help improve MS management. One possible alternative is to measure expansion of the spaces inside the brain, called the ventricles. This has advantages over whole-brain measures for personalised MRI monitoring, as it is more precise and analysis can be faster and automated.
However, we do not understand exactly how expansion of the ventricles (central brain loss) relates to MS lesions, inflammation and tissue damage; nor how useful it would be in individual management of MS progression. A new study published in Multiple Sclerosis Journal by Mr Samuel Klistorner from the University of Sydney has examined this question in detail.
What did the researchers do?
Fifty people with relapsing-remitting MS (48 taking disease-modifying therapies) underwent MRI and clinical assessment of disability at the study start and again after 1 and 5 years. Researchers measured changes in size and severity of old and new lesions; and changes in size of the ventricles (central brain loss) and the whole brain (whole brain loss).
What did the researchers find?
Between years 1 and 5, whole brain volume decreased by 1.55% on average, while the ventricles enlarged by 12.6%. Expansion of the ventricles (central brain loss) was significantly correlated with disability at the start of the study and with progression of disability during the study.
There was a significant increase in the volume of MS lesions during the study; with expansion of old lesions accounting for most of this increase (69.3%), as well as being the largest contributor to central brain loss.
Interestingly, previous studies have shown that in MS patients on disease-modifying therapies, expansion of old lesions is a better predictor of clinical progression than the formation of new lesions.
What does this mean for people with MS?
The hope is that, as a field, MRI in MS is not far from delivering sensitive measures of brain loss in MS that could be conducted yearly, so that people at risk of physical or cognitive progression of MS can be identified as early as possible. This would allow therapies to be adjusted or optimised in individuals and help to accurately assess the effect of new candidate drugs on MS progression in clinical trials.
Studies such as this are bringing us closer to this goal. Mr Klistorner has been awarded an MS Australia Postgraduate Scholarship commencing 2023 to further this work; you can read more about his new project here.